By Wayne Koberstein, executive editor
Somebody better be up to this challenge, or we’re all in trouble. With more and more reliance on large-molecule drugs, the injectables market has soared just as shortages due to product contamination, recalls, and plant shutdowns have plagued companies and patients. The two crises are intimately related, and only an industrywide surge in investment for facility upgrades, mainly by suppliers, will address them both.
From my earliest days in the pharmaceutical industry, production, storage, and distribution of parenterals have been the downfall of many companies. Typically, a Big Pharma will buy a smaller company with an injectables line. Boom — within a year, the inspectors descend on the acquired facilities and lock them down. Headlines declare the company’s complacency toward product quality and patient safety. The company defends itself, shifting as much blame as possible to the company it acquired, as if it were just another innocent injured party in the unfortunate affair.
Eventually large companies, presumably exhausted from repeating the experience with such acquisitions, began to rely increasingly on third-party suppliers. One effect was to spread drug production globally; many of the great pharma production centers in the United States and Europe have since closed in favor of outsourced manufacturers in India and other farflung facilities. CMOs took over some of the abandoned capacity in the West but followed the general trend toward worldwide production. One major result was that the sheer number of plants far outgrew regulators’ ability to inspect and validate them. Lack of inspection is now a standard part of many suppliers’ business models — and if the pendulum were to swing toward greater enforcement as the FDA threatens, it would throw those companies into a financial sandtrap.
The technologies that can ensure the purity of parenterals have existed for some time. Prefilled syringes or autoinjectors offer a general solution. One specific platform is aseptic blow-fill-seal (BFS), which I have described in the past. Avoiding microbial contamination on the shop floor by isolating the product from personnel and other sources and sealing it against exposure to further contaminants in distribution are the central challenges. But any new system that requires retrofitting or de novo construction will mean capital expenditures a given supplier may be unable to make. So the question of who is up to the challenge is more about economics and finances than technologies.
Rewards For High Quality Are Likely In The Future
Regulators may yet apply enough pressure to force widespread investment in the needed technologies. But even those who put their faith in market forces would accept the inevitability of a major shakeout among suppliers over this issue. Sooner or later, regulators and customers will find ways to punish the poor-quality producers and lax distributors responsible for adulterated or counterfeited products, or related breakdowns in supply. There will be rewards as well for the suppliers who survive by maintaining or upgrading their production lines.
One obvious reward would be entry into the burgeoning market for prefills. Prefilled injectors not only ensure sterility in manufacturing and distribution, but also cross-contamination between patients or providers at the point of care. Their ease of use, stability, and safety have created a growing demand and preference for them over traditional injectables.
Other incidental benefits may also apply with prefills. One is materials saving due to reduction or elimination of overfilling — one article I read claimed 20% more product yield because vials typically require the same percentage of overfill. Increased speed and flexibility of prefill production lines is another potential advantage. Prefill lines are also subject to greater automation, simplified cleaning, and less down time than traditional injectables.
Still, I can’t help but believe that the most compelling reason to adopt prefills is to upgrade the supply chain to a higher level of cleanliness. Yes, simple cleanliness should be the hallmark of any medical facility or organization. The rewards thus seem identical to the solution.
Is A Higher Standard On The Horizon?
Make no mistake, however — for many suppliers, low cost is their main or only selling point. Any technology that increases production costs or capital outlays pinches precious margins. To some extent, the entire existence of the generics industry depends on low-cost production and supply. But it doesn’t necessarily follow that poor-quality injectables must be the norm. If suppliers that cannot manage to maintain sterility of facilities, equipment, and product drop out of the game, a higher standard will apply to all the players that remain. Prices and margins will adjust accordingly.
Change May Not Come Soon Enough
Raising the bar for parenteral suppliers may come about without government pressure, but I doubt it. Yes, there is plenty of market pressure, but perhaps a bit too much on both sides of the issue. The recalls and drug shortages that make the news push producers toward the light of a higher standard; the economics toward the dark shadows of cut-rate production.
An echo exists in the question as well — the now age-old struggle between the innovative and the follow-on sides of the industry. Innovation may impel a more progressive approach to new technologies, on the assumption that generics inherently promote the opposite. But ours is a cut-and-paste industry; there are no longer only two distinct camps working in opposition. These days you see Big Pharmas with generics divisions, specialty pharma, new drug-delivery approaches, prospective biosimilars, and every shade in between — all arguably favoring widespread adoption of technologies that ensure purity of parenterals.
If you doubt my argument, or indeed accept it, a reliable test for it exists: time. Time will speak the final word on whether suppliers move widely to raise the standards for parenterals, spending what is necessary for prefill and other technologies to ensure sterility and supply from production to point of injection. My somewhat educated guess is that the change will not come soon enough or spread widely enough to save a great number of suppliers from a degraded fate. To the extent such a fallout occurs, we all stand the chance of suffering the consequences, as professionals or as patients.